One of the promising directions in schizophrenia research is the search for genetic markers of the disorder, biologically-based characteristics that identify individuals with a genetic predisposition for schizophrenia. Attention dysfunction is a strong candidate as a genetic marker for schizophrenia because the attentional abnormalities that are a central symptom of acute schizophrenia have been found in both chronic schizophrenics in symptom remission and in children with a schizophrenic parent. However, a measure of this attentional dysfunction that is independent of global processing deficits and specific to schizophrenia is needed. A new visual information processing task that-measures expectation-based selectivity has the potential to fill this gap. The principal objective of the proposed research is to investigate defective attentional selectivity as a potential genetic marker for schizophrenia. We plan to use cognitive and neurophysiological measures of selective attention to phenotype large pedigrees with multiple incidence of schizophrenia in order to determine whether defective selectivity is linked to the same gene(s) that convey risk for schizophrenia. Study 1 will identify that combination of cognitive and neurophysiological measures which optimizes the distinction between normal and abnormal attentional selectivity. Study 2 will use this combination of measures in a longitudinal study to establish that defective selectivity is a trait marker specific to schizophrenia rather than a state- dependent abnormality associated with psychosis. Study 3 will examine ten large families with a high rate of schizophrenia for abnormal attentional selectivity. These families are currently being genotyped for schizophrenia in a study being conducted by Dr. William F. Byerley in collaboration with the Howard Hughes Medical Institute. Defective selectivity will then be investigated as a phenotypic expression of genes transmitting risk for schizophrenia.